Restenosis rates following vascular interventions still limit their long-term success. Oxidative stress plays a relevant role in this pathophysiological phenomenon, but less attention has been devoted to its effects on DNA damage and to the subsequent mechanisms of repair. In the present study, we analysed in a model of arteriotomy-induced stenosis in rat carotid arteries the time-dependent expression of DNA damage markers and of DNA repair genes, together with the assessment of proliferation and apoptosis indexes. The expression of the oxidative DNA damage marker 7,8-dihydro-8-oxo-2′-deoxyguanosine was increased at 3 and 7 days after arteriotomy, with immunostaining distributed in the injured vascular wall and perivascular tissue. Expression of the DNA damage marker phospho-H2A.X was less relevant, but increased from 4 h to 7 days after arteriotomy, with immunostaining prevalently present in the adventitia and, to a lesser extent, in medial smooth muscle cells at the injury site. RT (reverse transcription)–PCR indicated a decrease in eight out of 12 genes involved in the DNA repair machinery we selected from 4 h to 7 days after arteriotomy, with the exception of an increase in the Mutyh and Slk genes (P<0.05). Western blot analysis revealed a decrease in p53 and catalase at 3 days after arteriotomy (P<0.05). A maximal 7% of BrdU-positive cells in the endothelium and media occurred at 7 days after arteriotomy, whereas the apoptotic index peaked at 3 days after injury (P<0.05). In conclusion, our results highlight a persistent DNA damage, presumably related to a temporary decrease in the expression of the DNA repair machinery and of the antioxidant enzyme catalase, playing a role in stenosis progression.
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Research Article|
January 12 2010
DNA damage and repair in a model of rat vascular injury
Amalia Forte;
*Department of Experimental Medicine, Second University of Naples, Via L. De Crecchio 7, 80138 Naples, Italy
Correspondence: Dr Amalia Forte ([email protected]).
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Mauro Finicelli;
Mauro Finicelli
*Department of Experimental Medicine, Second University of Naples, Via L. De Crecchio 7, 80138 Naples, Italy
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Mario Grossi;
Mario Grossi
*Department of Experimental Medicine, Second University of Naples, Via L. De Crecchio 7, 80138 Naples, Italy
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Mariano Vicchio;
Mariano Vicchio
†Department of Cardiothoracic and Respiratory Sciences, Via L. Bianchi, 80131 Naples, Italy
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Nicola Alessio;
Nicola Alessio
*Department of Experimental Medicine, Second University of Naples, Via L. De Crecchio 7, 80138 Naples, Italy
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Pasquale Santé;
Pasquale Santé
†Department of Cardiothoracic and Respiratory Sciences, Via L. Bianchi, 80131 Naples, Italy
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Marisa De Feo;
Marisa De Feo
†Department of Cardiothoracic and Respiratory Sciences, Via L. Bianchi, 80131 Naples, Italy
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Maurizio Cotrufo;
Maurizio Cotrufo
†Department of Cardiothoracic and Respiratory Sciences, Via L. Bianchi, 80131 Naples, Italy
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Liberato Berrino;
Liberato Berrino
*Department of Experimental Medicine, Second University of Naples, Via L. De Crecchio 7, 80138 Naples, Italy
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Francesco Rossi;
Francesco Rossi
*Department of Experimental Medicine, Second University of Naples, Via L. De Crecchio 7, 80138 Naples, Italy
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Umberto Galderisi;
Umberto Galderisi
*Department of Experimental Medicine, Second University of Naples, Via L. De Crecchio 7, 80138 Naples, Italy
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Marilena Cipollaro
Marilena Cipollaro
*Department of Experimental Medicine, Second University of Naples, Via L. De Crecchio 7, 80138 Naples, Italy
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Publisher: Portland Press Ltd
Received:
August 05 2009
Revision Received:
September 18 2009
Accepted:
October 05 2009
Accepted Manuscript online:
October 05 2009
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2010 Biochemical Society
2010
Clin Sci (Lond) (2010) 118 (7): 473–485.
Article history
Received:
August 05 2009
Revision Received:
September 18 2009
Accepted:
October 05 2009
Accepted Manuscript online:
October 05 2009
Citation
Amalia Forte, Mauro Finicelli, Mario Grossi, Mariano Vicchio, Nicola Alessio, Pasquale Santé, Marisa De Feo, Maurizio Cotrufo, Liberato Berrino, Francesco Rossi, Umberto Galderisi, Marilena Cipollaro; DNA damage and repair in a model of rat vascular injury. Clin Sci (Lond) 1 April 2010; 118 (7): 473–485. doi: https://doi.org/10.1042/CS20090416
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